a. Field of the Invention
This invention relates to pyrrolobenzoxazines and pyrrolobenzothiazines derivatives. More particularly, this invention relates to heterocycles having a 4-substituted-4H-pyrrolo[2,1-c][1,4]-benzoxazine or a -benzothiazine nucleus, to processes for their preparation, to intermediates for the processes and to methods for using the pyrrolobenzoxazines and pyrrolobenzothiazines.
B. Description of the Prior Art
Interest to date in pyrrolo[2,1-c][1,4]benzoxazine and -benzothiazine derivatives have been exiguous. Only recently has the unsubstituted ring system, 4H-pyrrolo[2,1-c][1,4]benzoxazine, been synthesized, M. Artico, et al., J. Heterocycl. Chem., 8, 283 (1971). The compounds of the present disclosure are distinguished from the latter prior art compound by having substituents at a variety of positions on the nucleus, most notably at position 4 of the 4H-pyrrolo[2,1-c][1,4]benzoxazine and -benzothiazine ring system. Moreover, the synthesis reported by Artico, et al., is not suitable for preparing 4-substituted 4H-pyrrolo[2,1-c][1,4]benzoxazines since it elaborates the carbon atoms at position 4 of the pyrrolobenzoxazine from formaldehyde in a Mannich-type reaction. Prior pharmacologic interest in this class of heterocycles appears to be practically non-existant except for an investigation of certain 1,2,3,3a-tetrahydro-4-H-pyrrolo[2,1-c][1,4]benzoxazines as potential antitumor compounds, M. Artico, et al., 11 Farmaco, Ed. Sci., 24, 285 (1969). The latter compounds are distinguished readily from the compounds of the present invention by being cyclic amides with an additional carbonyl function adjacent to the cyclic oxygen; such carbonyl and amide functions being absent in compounds of the present invention.
Notwithstanding the previous limited interest in pyrrolobenzoxazoles and pyrrolobenzothiazines, we now have found a class of 4H-pyrrolo[2,1-c][1,4]benzoxazines and benzothiazines having useful pharmacologic and therapeutic properties.